The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China; Department of Ophthalmology, Northern Jiangsu People's Hospital, Yangzhou, China.
Genomics. 2023 May;115(3):110615. doi: 10.1016/j.ygeno.2023.110615. Epub 2023 Mar 17.
Wet age-related macular degeneration (wAMD) is the leading cause of blindness among the elderly in industrialized nations. Anti-vascular epidermal growth factor (VEGF) therapy via intravitreal injection is the most effective clinical treatment for wAMD due to high concentrations of VEGF that promote choroidal neovascularization. While PIWI proteins participate in various biological processes, their function in AMD remains unclear. In this study, we discovered that PIWIL4 expression is elevated in a laser-induced choroidal neovascularization (CNV) model and that it regulates angiogenesis in vitro and in vivo. Differentially expressed piwi-interacting RNAs (piRNAs) were identified in a CNV model and were shown to potentially regulate angiogenesis via bioinformatics analysis. PIWIL4 knockdown inhibits VEGF secretion and VEGFR2 phosphorylation. Overall, PIWIL4 may serve as a novel target to block pathological choroidal neovascularization, and the study of the PIWI-piRNAs pathway in wAMD highlights its broad function in somatic cells.
湿性年龄相关性黄斑变性（wAMD）是工业化国家老年人致盲的主要原因。由于血管内皮生长因子（VEGF）浓度高，促进脉络膜新生血管形成，玻璃体内注射抗血管 VEGF 治疗是治疗 wAMD 最有效的临床方法。尽管 PIWI 蛋白参与各种生物学过程，但它们在 AMD 中的功能尚不清楚。在这项研究中，我们发现 PIWIL4 在激光诱导的脉络膜新生血管化（CNV）模型中表达上调，并且在体外和体内调节血管生成。在 CNV 模型中鉴定出差异表达的 piwi 相互作用 RNA（piRNA），并通过生物信息学分析表明其可能通过调节血管生成发挥作用。PIWIL4 敲低抑制 VEGF 分泌和 VEGFR2 磷酸化。总之，PIWIL4 可能成为阻断病理性脉络膜新生血管形成的新靶点，对 wAMD 中 PIWI-piRNA 通路的研究突出了其在体细胞中的广泛功能。
